Abstract Introduction Traditional risk factors for obesity and type 2 diabetes, such as poor diet and low physical activity, cannot fully explain the increased incidence of these diseases. Insufficient sleep and circadian misalignment due to shift work may contribute, in part, to this epidemic through their growing prevalence and associated impaired glucose regulation and eating out of phase. Methods Female nightshift healthcare workers (n=5) worked ≥2 shifts (~7pm-7am) during the 7-day study. Actigraphy was measured and participants wore continuous glucose monitors and completed three 24-hour dietary recalls. Dim light melatonin onset was predicted (pDLMO) for each worker from an actigraphy derived algorithm validated for shift workers. The timepoints two hours after (pDLMO+2) and 10 hours after (pDLMO+10) predicted DLMO are presented as a range in which sleep typically occurs, on average, relative to DLMO. Results Mean participant age was 30.7 years and body mass index 22.8 kg/m2. Dietary recalls report the average total energy consumed on workdays to be 1,653 kcal ± 444 (mean ± SD) compared to 1,517 kcal ± 421 on free days (p=0.64). Average eating windows were 13.88 ± 2.69 hours on nightshifts compared to 9.88 ± 1.82 hours on workfree days (p=0.051, n=4 one individual did not report eating while on shift). Further, eating occasions between 10pm–7:30am were only reported on worknights. Average pDLMO was 23.26 ± 1.27 hours, corresponding to the middle of shift. The average interstitial glucose level between pDLMO+2 and pDLMO+10 on shift was 88.4 mg/dL ± 9.0 and the average during the same interval on workfree nights was 81.1 mg/dL ± 7.0 (p = 0.024). Additionally, an increase in 24-hour average glucose was observed on shift 90.9 ± 4.9 compared to free days 86.1 ± 6.2 (p=0.021). Conclusion Early results from this ongoing study show that an extended eating window, eating overnight, and/or working overnight contribute to increased glucose levels while night workers are on shift compared to their days off. Increased overnight glucose levels, especially at a time the body may be accustomed to sleeping, represent a time of impaired glucose tolerance and potentially reduced insulin sensitivity. Support (if any) Anschutz CCTSI Pilot Grant Award, CTSA Grant UL1 TR002535
Objectives To determine whether a selective increase of visceral adipose tissue content will result in insulin resistance. Methods Sympathetic denervation of the omental fat was performed under general inhalant anesthesia by injecting 6‐hydroxydopamine in the omental fat of lean mongrel dogs ( n = 11). In the conscious animal, whole‐body insulin sensitivity was assessed by the minimal model ( S I ) and the euglycemic hyperinsulinemic clamp (SI CLAMP ). Changes in abdominal fat were monitored by magnetic resonance. All assessments were determined before (Wk0) and 2 weeks (Wk2) after denervation. Data are medians (upper and lower interquartile). Results Denervation of omental fat resulted in increased percentage (and content) of visceral fat [Wk0: 10.2% (8.5‐11.4); Wk2: 12.4% (10.4‐13.6); P < 0.01]. Abdominal subcutaneous fat remained unchanged. However, no changes were found in S I [Wk0: 4.7 (mU/l) −1 min −1 (3.1‐8.8); Wk2: 5.3 (mU/l) −1 min −1 (4.5‐7.2); P = 0.59] or SI CLAMP [Wk0: 42.0 × 10 −4 dl kg −1 min −1 (mU/l) −1 (41.0‐51.0); Wk2: 40.0 × 10 −4 dl kg −1 min −1 (mU/l) −1 (34.0‐52.0); P = 0.67]. Conclusions Despite a selective increase in visceral adiposity in dogs, insulin sensitivity in vivo did not change, which argues against the concept that accumulation of visceral adipose tissue contributes to insulin resistance.
Sleep is an essential factor for health and wellbeing in people across the age spectrum; yet many adolescents do not meet the recommended 8-10 h of nightly sleep. Unfortunately, habitually insufficient sleep, along with the metabolic changes of puberty, puts adolescents at increased risk for a host of adverse health outcomes such as obesity and type 2 diabetes (T2D). Furthermore, individuals from historically minoritized racial and ethnic groups (e.g. Hispanic/Latinx, African American/Black) are more likely to experience shorter sleep duration compared to adolescents of White/European origin, placing them at even greater risk for disparities in T2D risk.
The last 50–100 years has been marked by a sharp rise in so-called "Western-diseases" in those countries that have experienced major industrial advances and shifts towards urbanized living. These diseases include obesity, type 2 diabetes, inflammatory bowel diseases, and food allergies in which chronic dysregulation of metabolic and/or immune processes appear to be involved, and are likely a byproduct of new environmental influences on our ancient genome. What we now appreciate is that this genome consists of both human and co-evolved microbial genes of the trillions of microbes residing in our body. Together, host–microbe interactions may be determined by the changing diets and behaviors of the Western lifestyle, influencing the etiopathogenesis of "new-age" diseases. This review takes an anthropological approach to the potential interplay of the host and its gut microbiome in the post-industrialization rise in chronic inflammatory and metabolic diseases. The discussion highlights both the changes in diet and the physical environment that have co-occurred with these diseases and the latest evidence demonstrating the role of host–microbe interactions in understanding biological responses to the changing environment. Technological advances that have led to changes in agriculture and engineering have altered our eating and living behaviors in ways never before possible in human history. These changes also have altered the bacterial communities within the human body in ways that are seemingly linked with the rise of many intestinal and systemic metabolic and inflammatory diseases. Insights into the mechanisms of this reciprocal exchange between the environment and the human gut microbiome may offer potential to attenuate the chronic health conditions that derail quality of life. This article is part of a special issue on microbiota.
Insufficient sleep induces insulin resistance and is associated with an increased risk for developing obesity and cardiometabolic diseases, implicating sleep loss as a metabolic stressor. Fibroblast growth factor 21 (FGF21) is a hepatokine secreted in response to stress and is elevated in human obesity and diabetes. FGF21 expression can be induced by free fatty acid (FFA) activation of peroxisome proliferator‐activator receptor alpha. We previously reported that insufficient sleep results in elevated FFA; however, the impact of insufficient sleep on FGF21 has not been explored. In an ongoing study, we are comparing the effects of insufficient sleep on insulin sensitivity in physically active and inactive individuals to determine whether regular exercise attenuates the adverse effects of insufficient sleep. To explore the effects of physical activity and insufficient sleep on FGF21, we compared changes in FGF21 during an oral glucose tolerance test (OGTT). Eleven sedentary (SED: 6F, 24.9±4.2y, 22.3±1.7kg/m 2 ; mean±SD) and 11 physically active adults (PA: 6F, 23.5±3.3y, 22.0±2.3kg/m 2 ) participated in a 6‐day controlled inpatient protocol. Participants were provided isocaloric diets designed to meet energy requirements. Active participants continued to exercise during insufficient sleep by conducting 60 minutes of moderate physical activity (treadmill running) at 65–75% of maximum heart rate. An OGTT was conducted at baseline (9h sleep opportunity/night) and after 3 nights of insufficient sleep (5h sleep opportunity/night). Blood was sampled at T=0, +30, +60, +90, and +120 minutes following glucose ingestion and assayed for FGF21, glucose, insulin and FFA. FGF21 was elevated in response to insufficient sleep in PA participants (Fig 1a; baseline: 40.5±13.3 v. insufficient sleep: 95.3±18.2 pg/ml, p<0.05), but not SED (baseline: 68.9±19.4 v. insufficient sleep: 95.6±24.1 pg/ml, p=ns). Both SED and PA participants displayed elevated glucose in response to the OGTT during insufficient sleep (Fig 1b), whereas insulin was elevated only in SED participants (Fig 1c). PA participants had higher levels of FFA as compared to SED, though FFA were not altered by insufficient sleep in either group (Fig 1d). Changes in FGF21 were not related to glucose, insulin or FFA. FGF21 is elevated during insufficient sleep in physically active individuals. Furthermore, insulin response to an OGTT during insufficient sleep was attenuated only in the physically active participants. Though the physiological implications of elevated FGF21 in humans are unclear, we speculate that elevated FGF21 during insufficient sleep in active individuals may act as a compensatory response to mitigate metabolic impairments. Support or Funding Information This work was supported by the Sleep Research Society Early Career Development Award, the National Institutes of Health GCRC grant RR‐00036, R01HL109706 and K01DK110138, Society in Science, and The Branco Weiss Fellowship, administered by the ETH Zürich. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Abstract Introduction Shift work is associated with sleep and circadian disruption, which may have adverse effects on the gut microbiome. However, little is known about the relationship between shift work and the gut microbiome in free-living humans. In this study, we aimed to investigate whether shift work detrimentally impacts the gut microbiome. Methods Day- and night-shift workers were recruited from clinical settings. Mann-Whitney tests were used to compare alpha-diversity (Inverse Simpson), beta-diversity (Bray-Curtis dissimilarity), and taxa relative abundance between groups. Percent differences are reported for taxa that differed based on Mann-Whitney tests (P< 0.05). Because these analyses are preliminary, unadjusted p-values are presented. Results Six night- (83% female, age 29 ± 2.5) and six day-shift (50% female, age 33 ± 6.8) workers were included. Mean alpha-diversity was 9.0 among day-shift workers and 8.1 among night-shift workers (P=0.64). Shift work explained 8.5% and 9.7% of variability in genera and species beta-diversity, respectively (P=0.50, 0.38). Night-shift workers had 102% higher mean relative abundance of Intestinimonas (P=0.04), while day-shift workers had 99% higher relative abundance of Mogibacterium (P=0.01). Day-shift workers had 79% higher mean relative abundance of Mogibacterium diversum (P=0.02), while night-shift workers had 87% higher relative abundance of Streptococcus suis (P=0.04) and 108% higher relative abundance of Treponema succinifaciens (P=0.02). Conclusion This study provides preliminary evidence that shift work may be associated with alterations to the gut microbiome. For example, we observed differences in the abundance of Intestinimonas and Mogibacterium. Intestinimonas is a butyrate-producing microbe, with anti-inflammatory effects, while Mogibacterium is thought to be deleterious to gut health. These associations are in the opposite direction than we expected, perhaps because participants were from a healthy population and this is a compensatory mechanism, though further exploration is needed. Future analyses will examine the functional potential of the gut microbiota in day- vs. night-shift workers. Support (if any) Anschutz CCTSI Pilot Grant Award, CTSA Grant ULI TR002535, Transdisciplinary Training Grant in Sleep and Circadian Research (T32 HD007014), Office of Naval Research MURI grant N00014-15-1-2809.
